基于代谢组学的蒙古扁桃药材抗大鼠肾纤维化作用机制研究

Investigation of the anti-renal fibrosis effect of Amygdalus mongolica using metabonomics

运用代谢组学技术探究蒙古扁桃总提物抗大鼠肾纤维化可能的作用机制及代谢通路。将大鼠按体重随机分为模型组(MOD)、假手术组(SDG)、盐酸贝那普利组(benazepril hydrochloride,BHT)和蒙古扁桃总提物低(TOT-L)、中(TOT-M)、高(TOT-H)剂量组,每组10只,造模成功后连续灌胃给药3周后取大鼠肾脏及血样,样本处理后进行药效学研究及超高效液相色谱-四级杆串联飞行时间质谱(UPLC-Q-TOF/MS)分析。结果显示,蒙古扁桃总提物具有抗大鼠肾纤维化的作用;与模型组相比,蒙古扁桃总提物低、中、高剂量组可分别回调67、69、70个差异代谢物,共同回调62个差异代谢物,其中可通过回调S-腺苷甲硫氨酸、鸟氨酸和二酮古龙酸等7个与肾纤维化相关的关键生物标志物,进而参与精氨酸和脯氨酸代谢与戊糖和葡萄糖合成等5条代谢通路,发挥其抗肾纤维化的作用。本研究从代谢物角度阐述了蒙古扁桃药材抗大鼠肾纤维化的作用机制。动物实验经内蒙古科技大学包头医学院医学伦理委员会批准(批准号:20190314)。

Metabonomics techniques were used to investigate the mechanism and metabolic pathways of total extract of Amygdalus mongolicus against renal fibrosis in rats.Rats were randomly divided into a model group(MOD),a sham surgery group(SDG),a benazepril hydrochloride-treated group(BHT)and three groups treated with the total extract of Amygdalus mongolicus:low-dose group(TOT-L),middle-dose group(TOT-M)and highdose group(TOT-H),with 10 rats in each group.The rats were given intragastric administration for 3 weeks and kidney and blood samples were taken.Pharmacodynamic studies and ultra performance liquid chromatographyquadrupole time of flight-mass spectrometry(UPLC-Q-TOF/MS)analysis were used to show that the total extract of Amygdalus mongolicus has an anti-fibrotic effect in rats.Compared with the MOD group,rats in the TOT-L,TOT-M and TOT-H groups showed a reversal in 67,69,and 70 biomarkers,respectively,and shared 62 biomarkers.Reversal was observed for 7 key biomarkers related to renal fibrosis,including S-adenosy-L-methioninamine,ornithine,diketogulonic acid,and others,and changes in 5 metabolic pathways,including arginine and proline metabolism,pentose and glucuronate interconversions.These results give evidence of the metabolic pathways and the mechanism of action of Amygdalus mongolicus to prevent renal fibrosis in rats.The animal experiments were approved by the Medical Ethics Committee of Baotou Medical College(No.20190314).